tbuckley/cabot-search huggingface dataset:
Surgery for urologic cancers after SARS-CoV-2 infection: Adverse outcomes and optimal delay.
Authors: Madelyn Anne Flitcroft, Nathaniel Verhagen, Nayan Shah, Scott Johnson, Anai Kothari
Journal: Journal of Clinical Oncology (2023)

484 Background: Perioperative SARS-CoV-2 infection has been associated with increased adverse outcomes. Research conducted early in the COVID-19 pandemic suggested an 8 week delay after SARS-CoV-2 infection prior to undergoing surgery. The aim of this study is to determine if prior COVID-19 infection is an independent risk factor for adverse outcomes following surgery for urologic cancers. A secondary objective was to determine the optimal duration to delay surgery, specifically cystectomy, prostatectomy, or nephrectomy, after COVID-19 infection. Methods: Data from the National COVID Cohort Collaborative (N3C) data enclave was used to conduct this retrospective cross-sectional study. Patients with cancer diagnoses that underwent surgery for urologic cancers after January 2020 were included in the analyses. Urologic surgeries were queried using standard SNOMED concepts corresponding to cystectomy, nephrectomy, and prostatectomy. Patients were assessed for adverse postoperative events that were defined using standard SNOMED clinical concepts. COVID-19 positive patients were identified via the N3C Knowledge Store using positive lab measurement or a positive SARS-CoV-2 diagnosis. Analyses were conducted in the N3C data enclave. Results: The study cohort included 38,974 total patients with 15,216, 14,778, and 8,980, undergoing cystectomy, prostatectomy, and nephrectomy, respectively. 2,807 had a history of COVID-19 infection greater than 20 days prior to surgery. Prior history of COVID-19 was independently associated with adverse outcomes for cystectomy (OR 1.21 [1.03-1.43], p&lt;0.05) and nephrectomy (OR 1.27 [1.06-1.52], p&lt;0.05), but not prostatectomy (OR 1.14 [0.95-1.36]). Multivariable regression assessing time to surgery and risk for any adverse events, did not reveal significant benefit to waiting greater than 20 days after COVID-19 infection to operate. Conclusions: Patients with known prior COVID-19 infection who underwent surgical treatment of urologic cancers experienced increased risk of adverse surgical outcomes. Among this group, those who delayed surgery greater than 20 days after infection did not demonstrate decreased risk of these negative outcomes across the procedures studied. Optimal surgical delay in the treatment of urologic cancers after COVID-19 infection does not appear to be greater than 20 days.
Economic impact of bladder cancer (BC) in the United States (US).
Authors: Otavio Clark, Tulio Sarmento, Anthony Eccleston, Julia Brinkmann, Renato Picoli, Vamsi Daliparthi, Jorine Voss, Sanjana Chandrasekar, Allison Thompson, Jane Chang
Journal: Journal of Clinical Oncology (2023)

479 Background: Incidence and mortality for BC has changed very little over the past 20 years. Approximately 40% of patients with high-risk non-muscle invasive BC eventually recur/progress. It is important to understand the economic impact of disease recurrence/progression in BC. Methods: An economic model was constructed to calculate the number of patients receiving each treatment modality at every stage of disease and their respective costs. Epidemiological data was based on the CancerMPact Patient Metrics (PM) database, and treatment modality data retrieved from CMP Treatment Architecture (TA), 2021 version. Resource utilization and costs were obtained from the medical literature and public data sources. Only direct costs were considered. Results: There were an estimated 83,532 newly diagnosed BC patients of all stages in 2021 with a projected total cost of treatment of $2,584,783,728. Average cost per patient varied from $19,521 (stage 0a) to $169,533 (metastatic disease) (Table). Cost profile differed substantially among the stages of disease. For the 75,760 patients that were expected to have a recurrence in 2021, an additional cost of $3,953,096,316 was estimated at an average cost per patient of $52,179. The expected total cost to treat newly diagnosed and newly recurrent patients is reported in this model, with the total cost in 2021 estimated to exceed $6.5 billion. Conclusions: Treatment and resource costs increase for BC as the disease recurs/progresses. More effective treatments earlier in the disease setting to delay recurrence/progression may reduce the economic burden associated with BC. [Table: see text]
Neoadjuvant platinum-based chemotherapy for clinically node-positive penile squamous cell carcinoma: An international, multicenter, real-world study.
Authors: Kyle M. Rose, Darren Sanchez, Arfa Mustasam, Reagan Sandstrom, Kathryn Marchetti, Niki Marie Zacharias, Lance C. Pagliaro, Constantine Alifrangis, Kelvin A. Moses, Maarten Albersen, Eduard Roussel, Viraj A. Master, Bassel Nazha, Tony Zhuang, Jeffrey S. Montgomery, Chris Protzel, Marcos Tobias Machado, Philippe E. Spiess, Curtis Alvin Pettaway, Jad Chahoud
Journal: Journal of Clinical Oncology (2023)

9 Background: The efficacy of neoadjuvant platinum-based chemotherapy (NAPC) in penile squamous cell carcinoma (PSCC) was provided by small clinical trials, leaving clinicians with scant evidence-based guidance. Thus, we aimed to analyze real-world outcomes of patients with PSCC who received NAPC prior to surgical resection. Methods: Patients from 9 tertiary care centers who had undergone NAPC prior surgical resection for PSCC were included with locally advanced (cTany, cN+), non-metastatic (M0) disease. The primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS), Response was determined via best overall response measured with RECIST 1.1 criteria. Results: 167 patients were included, 137 (84%), of which received TIP prior to surgical resection. Ninety-two (55%) patients died during follow up, and the mean follow up for survivors was 57 months. The median OS was 42 months, while the median PFS was 17 months. The table details the response rates to NAPC, the associated survival, and Cox Proportional Hazards Modelling of OS and PFS. Predictors for OS and RFS included lymphovascular invasion, positive number of lymph nodes, extranodal extension, downstaging, best overall response, and ypN status. Figure 1 demonstrates OS outcomes by RECIST best response after chemotherapy, presence of downstaging after NAPC, ypN stage, and presence of extranodal extension. Conclusions: Upfront NAPC is effective in patients with lymph node metastases from penile carcinoma. Unsurprisingly, patients who demonstrated a robust response to therapy had improved survival outcomes compared to those who had not—as measured by RECIST criteria, tumor downstaging, pN staging, and presence of extranodal extension. This study represents the largest conglomeration of multi-institutional penile carcinoma patients treated with NAPC, and provides further supportive data for multimodal therapy for advanced penile cancer patients while prospective clinical trials complete accrual. [Table: see text]
Testicular radiomics correlated with pathology at time of post-chemotherapy retroperitoneal lymph node dissection for non-seminomatous germ cell tumor.
Authors: Jacob Taylor, Nikit Venishetty, Yin Xi, Jeffrey Howard, Yee Seng Ng, Aditya Bagrodia
Journal: Journal of Clinical Oncology (2023)

413 Background: Testicular germ cell tumors are the most commonly diagnosed malignancy in men aged 20 to 39 years old. Up to a third of patients will have metastatic disease at presentation typically managed with upfront chemotherapy. For many patients with metastatic non-seminomatous germ cell tumor (NSGCT), post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) is performed to further stage and treat residual disease in the retroperitoneum. Although 50% of patients will have viable GCT or teratoma, we do not have accurate tools to predict pre-operatively which patients will have residual disease after chemotherapy. Testicular radiomics is an emerging field that collects complex quantitative tumor imaging data from conventional imaging to aid in clinical decision making. Our aim was to use testicular radiomics data to predict pathology after PC-RPLND. Methods: We extracted radiomics data on 45 patients with metastatic NSGCT undergoing PC-RPLND from 2008-2019. Clinical and pathologic data were collected. Regions of interest (ROI) around metastatic nodes were drawn by a dedicated abdominal radiologist. PyRadiomics, an open-source imaging extraction software, was used to extract first order, shape, and second order statistics from each ROI. Multiple t-tests of testing difference in radiomic features between binary pathology type were performed. P values were adjusted using the BH method to control false discovery rate. Boxplot of features with adjusted p value &lt; 0.05 were shown. Radiomic feature extraction was done in python 3.7 and statistical analyses were done in R 4.2.0. Results: There were 16 (36%) clinical stage II patients and 28 (62%) clinical stage III. 19 (42%) patients had necrosis on PC-RPLND pathology, while 24 (53%) and 2 (4%) patients had teratoma and viable germ cell tumor, respectively. First order statistics mean, median, 90 th percentile and root mean squares were significant. Strong correlations were observed between these four features and a lower signal was associated with positive pathology (Table). No significant difference was observed in other first order, shape, or texture features. Conclusions: Testicular radiomics is an emerging tool that has the potential to help predict which patients with metastatic NSGCT are at higher risk of persistent disease after chemotherapy. This study found relatively few first order radiomic data that were correlated with post-operative pathology. Further precision of extraction of the radiomics data may improve clinical decision-making in patients with metastatic NSGCT after chemotherapy prior to RPLND. [Table: see text]
Real-world use of darolutamide, enzalutamide, and apalutamide for non-metastatic castration-resistant prostate cancer (DEAR).
Authors: Daniel J. George, Nasreen Khan, Niculae Constantinovici, Javeed Khan, Guifang Chen, Julie Xu, Jorge A. Ortiz, Alicia K. Morgans
Journal: Journal of Clinical Oncology (2023)

332 Background: Second-generation androgen receptor inhibitors (ARIs) are the preferred treatment for patients (pts) with non-metastatic castration-resistant prostate cancer (nmCRPC). In this setting, an important therapeutic goal is to minimize adverse events (AEs) and prolong time on ARI treatment. This is the first study to assess real-world (RW) utilization and outcomes of all currently available ARIs, darolutamide (daro), enzalutamide (enza), and apalutamide (apa) in pts with nmCRPC. Methods: DEAR (NCT05362149) is a retrospective observational chart review using electronic medical records from the Precision Point Specialty network of US urology practices. Eligibility criteria included nmCRPC diagnosis, no previous treatment with a novel hormonal agent, and ARI treatment initiation for the first time from August 2019 to March 2022. Pts were classified into 3 cohorts based on the first prescribed ARI in the nmCRPC stage. We present an interim report including the primary composite endpoint (DIS/MET): proportion of pts who discontinued initial ARI treatment (DIS) or progressed to metastasis (MET); and secondary endpoints: time to DIS/MET and underlying reasons. Results: In total, 666 pts were included (daro/enza/apa, n=276/280/110). The proportion of pts starting treatment with daro increased during the study period relative to enza or apa, which declined or remained stable, respectively. Median age (80/79/80 years), White race (68%/69%/74%) and median PSA doubling time (6.7/6.0/7.8 months) at baseline were similar in the daro/enza/apa cohorts, respectively. Median length of follow-up was similar. Fewer pts had a DIS/MET event during the study in the daro cohort (35.9%), compared with enza or apa (52.1%/50.9%); this trend was seen within 6 to 18 months after ARI start. Median time to DIS/MET was 33.4/20.8/18.5 months for daro/enza/apa, respectively. Most common reasons for DIS/MET in the daro/enza/apa cohorts were AEs (8.3%/15.0%/12.7%), death (3.3%/5.4%/2.7%), and MET (14.9%/22.9%/18.2%). Conclusions: This RW study in the US shows that, despite similar baseline characteristics, fewer nmCRPC pts treated with daro had DIS/MET (especially due to AEs/MET) versus enza and apa, and the time to this event was longer in the daro cohort. These findings may be attributed to daro being a structurally distinct ARI with low potential for blood–brain barrier penetration. [Table: see text]
Radical nephroureterectomy followed by adjuvant chemotherapy (RNU-AC) versus observation (RNU-O) in early-stage upper urinary tract cancers with variant histology (UUTC-VH).
Authors: Karan Jatwani, Vasanthan Muthusamy Kumarasamy, Arya Mariam Roy, Kristopher Attwood, Anthony George, Muhammad Salman Faisal, Stuthi Perimbeti, Gurkamal S. Chatta, Dharmesh Gopalakrishnan
Journal: Journal of Clinical Oncology (2023)

487 Background: Upper urinary tract cancers (UUTC) are less frequent and associated with poorer stage-for-stage prognosis compared to bladder cancer, with variant histology being an independent predictor of inferior outcomes. The POUT trial included only patients with predominantly urothelial tumors. We aimed to compare outcomes among patients with UUTC-VH who were treated with RNU-AC vs. RNU-O. Methods: We queried the National Cancer Database for adult patients with UUTC-VH diagnosed between 2004 and 2018. Only patients who underwent RNU with node-negative disease on pathological staging (pT2-4N0M0) were included and divided into two groups based on the postoperative treatment strategy - RNU-AC and RNU-O. Patients who received neoadjuvant chemotherapy were excluded from analyses. Fisher’s exact and Mann Whiney U tests were used to compare frequency distributions. Cox Proportional Hazards regression was employed for multivariate analysis of factors associated with overall survival. Models were adjusted for age, sex, race, income, educational level, clinical T stage, insurance status, and the Charlson Comorbidity Index. Results: A total of 522 patients were identified – 133 (25.5%) received RNU-AC while 389 (74.5%) underwent RNU-O. Patients in the RNU-AC group were younger (median 69 vs. 76 years, P &lt;0.001). Patients with small cell (15.8% vs 4.9%), micropapillary (9.8% vs 5.9%) and adenocarcinoma (9% vs 6.7%) histologies were more likely while those with squamous histology was less likely to receive AC (38.3% vs 50.6%) (p &lt; 0.001 for all comparisons). A significant majority of patients in each T stage were treated with AC – 87.1% of pT1, 73.2% of pT2, and 68.4% of pT3 (P = 0.009). Overall survival in the RNU-AC and RNU-O groups were comparable (median of 27 vs 24.1 months, log rank-P = 0.63). On multivariable analysis, neither AC nor histological subtype were not independently predictive of OS (HR for AC = 0.96, 95% CI 0.74-1.24, P = 0.75). Conclusions: This is the largest study to date evaluating outcomes with AC after RNU in UUTC-VH since these patients were largely excluded from AC clinical trials. We observed that AC was not associated with improved overall survival after RNU in this population.
Effect of treatment of residual disease after immunotherapy-based combinations on complete response rate in metastatic renal cell carcinoma.
Authors: Fabien Moinard-Butot, Marine Oriel, Thibault Tricard, Roberto Luigi Cazzato, Laure Pierard, Victor Gaillard, Pierre Werle, Veronique Lindner, Sophie Martin, Caroline Schuster, Catherine Roy, Mickael Burgy, Anne Anthony, Cecile Bigot, Philippe Boudier, Aurelie Fritsch, Gabriel G. Malouf, Herve Lang, Philippe Barthelemy
Journal: Journal of Clinical Oncology (2023)

601 Background: Immunotherapy (IO) has revolutionized the management of metastatic renal cell carcinoma (mRCC) by improving survival, overall response and complete response (CR) rates. CR is achieved in 11 to 17% with the different PD-1-based IO combinations in first-line setting of mRCC. However, local treatment of residual disease after systemic treatment exposure may improve CR rates. We performed a retrospective study to characterize patients (pts) in CR with systemic therapy alone or combined to an ablative approach of residual disease. Methods: We included all consecutive mRCC pts treated with mRCC in first-line treatment with IO combination with IO or TKI, either alone or with local treatment at the Institut de Cancérologie Strasbourg Europe. Pts were characterized according to IMDC risk group. Radiologic response was defined according to RECIST v1.1. Results: We enrolled 80 pts with mRCC between 5/2015 and 5/2022; median age was 68 (41-89) years; 75% male; 36 pts (45%) had prior nephrectomy; IMDC risk group: 12 favorable (15%), 50 intermediate (63%), 18 poor risk pts (22%), respectively; 47 pts (59%) received IO + IO, 24 (30%) received IO + TKI and 9 pts (11%) received another IO-based therapy; 35 pts (44%) achieved partial response, 23 pts (29%) stable disease, 13 pts progressive disease and 9 pts achieved CR (11%) as best response with systemic therapy alone; 10 pts out of 35 PR pts achieved CR by adding local treatment on residual disease. Among CR pts: 5 out of 19 pts had a component of sarcomatoid histology; median age was 60 years. Characteristics of pts with CR are reported in the table. Median duration of IO exposure before local therapy was 13 months. Residual disease resected sites included kidney (N = 6), lymph node (N = 4), lung metastasis (N = 2) and liver metastasis (N = 1). Local treatment was surgery for 9 pts and liver thermoablation for 1 patient. Conclusions: The resection of residual disease after first line IO-based therapy in mRCC improves CR rates (from 11% up to 24%). This approach should be considered as an option for a selected population. Prospective trials assessing this strategy should be performed in the future. Characteristics of patients in CR. [Table: see text]
Neoadjuvant pembrolizumab for cisplatin-ineligible muscle-invasive bladder cancer prior to radical cystectomy.
Authors: Kyle M Rose, Marco Bandini, Heather L Huelster, Giuseppe Basile, Shreyas U Naidu, Philippe E. Spiess, Andrea Necchi, Roger Li
Journal: Journal of Clinical Oncology (2023)

513 Background: There is an unmet need for systemic treatment options in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based neoadjuvant chemotherapy. The PURE-01 trial has also demonstrated preliminary efficacy when pembrolizumab is used in the neoadjuvant setting. We aimed to compare pathologic response and survival outcomes in cisplatin-ineligible patients receiving neoadjuvant pembrolizumab (NAP) vs. immediate radical cystectomy (IRC). Methods: Cisplatin-ineligible MIBC patients were identified from the PURE-01 trial and compared against cisplatin-ineligible MIBC patients treated with immediate radical cystectomy (IRC). Overall survival was analyzed using Kaplan-Meier and Cox Proportional Hazards Modelling. IRC patients were matched via nearest neighbor propensity technique to cisplatin-ineligible patients from PURE-01 by ECOG status, GFR, age, sex, and clinical T stage. Results: Thirty-nine cisplatin-ineligible patients treated with NAP were identified from PURE-01, and compared against 313 cisplatin-ineligible patients undergoing IRC (Figure 1A). OS was prolonged in the NAP patients, with median survival of 19 months in the IRC vs. not reached (NR) in the NAP group (p=&lt;0.01). Following nearest neighbor matching, 39 patients were identified from the IRC cohort, with comparable baseline clinicopathologic variables as listed in the table. Patients receiving NAP experienced a higher complete response rate on final pathology (pT0: 33% vs. 13%, p=0.03). Median OS was prolonged in the propensity score matched analysis (NAP NR vs. IRC 21.0mo, p&lt;0.01), specifically at 12mo (89% vs. 57%), 24mo (64% vs. 28%), and 36 months after surgery (33% vs. 13% ) (p&lt;0.01). Compared to NAP, cisplatin-ineligible patients undergoing IRC experienced worse OS, with a Hazard Ratio of 2.0 (95% CI 1.1 - 3.89). Conclusions: Cisplatin-ineligible patients receiving NAP for muscle invasive bladder cancer had a higher rate of downstaging and a survival advantage over patients who underwent IRC. Although this study suggests promising systemic options for cisplatin-ineligible patients in the neoadjuvant setting, results of ongoing prospective randomized trials will help validate these findings and provide therapeutic options to cisplatin-ineligible patients. [Table: see text]
Source of funding and enrollment disparity in prostate cancer (PCa) clinical trials.
Authors: Irbaz Bin Riaz, Syed Arsalan Ahmed Naqvi, Mahnoor Islam, Waleed Ikram, Kaneez Zahra Rubab Khakwani, Hafsah Ijaz, Ahsan Ayaz, Parminder Singh, Alan Haruo Bryce
Journal: Journal of Clinical Oncology (2023)

40 Background: Previously we have reported enrollment disparities in PCa clinical trials. Funding source can influence minority representation in clinical trials. Hence, we aimed to evaluate the impact of source of funding on enrollment disparities in PCa clinical trials. Methods: MEDLINE and EMBASE were searched to identify phase II/III PCa trials. All relevant trials reporting age by 65 years were considered eligible for inclusion. Trials recruiting from the United States (US) were considered eligible for analysis by race and ethnicity. The trial proportions of age, or racial/ethnic subgroup category and the global incidence in the corresponding age subgroup (from the global burden of disease database), or the US-population-based incidence in the corresponding racial/ethnic subgroup (from SEER 21 database) were used to compute enrollment incidence ratio (EIR) at each trial. EIRs with corresponding 95% confidence intervals (CI) were then meta-analyzed using a random-effects model and stratified by sources of funding (industry, US-government, and others [academic and non-US govt]). A univariate meta-regression was conducted to assess the temporal changes in EIR by each funding category. Results: Of 127 trials recruiting from the US, 89 (70%) reported race, and 35 (27%) reported ethnicity. Among those, 57 (64%), 14 (16%), and 18 (20%) trials reported industry, US-government, and other sources of funding, respectively. Of those reporting ethnicity, 23 (66%), 4 (11%), and 8 (23%) trials reported industry, US-government, and other sources of funding, respectively. Among the 287 eligible trials, 49 trials (17%) reported age by 65 years. Of those, 36 (73%), 6 (12%), and 7 (13%) reported industry, US-government, and other sources of funding, respectively. In terms of racial/ethnic enrollment, Black patients were significantly under-represented in industry funded trials (0.33; 0.27-0.41). No significant disparity was observed in US-government funded trials (0.75: 0.57-1.00). The P-value of interaction was &lt;0.0001. Hispanics were significantly under-represented in industry funded clinical trials (0.56; 0.43-0.74). The number of US-government funded trials reporting Hispanics were small (&lt;10) which precluded any meaningful statistics. No significant disparity was observed in terms of older adults (EIR: 1.00; 95% CI: 0.95; 1.05) overall and by funding sources. Black patients’ representation in industry funded PCa trials has significantly decreased over the last three decades. No significant change was observed in US-government funded PCa trials over the last three decades (P:0.004). Conclusions: Black and Hispanic men with PCa are likely to be under-represented in industry sponsored clinical trials. Black patients’ representation in industry sponsored trials has declined over time, thus widening the cancer-care inequities in these patients.